Study of ACE-031 in Subjects With Duchenne Muscular Dystrophy

• ClinicalTrials.gov Identifier: NCT01099761
• Recruitment Status: Terminated
• First Posted: April 8, 2010
• Results First Posted: October 14, 2016
• Last Update Posted: April 5, 2017
• Sponsor: Acceleron Pharma Inc.
• Information provided by (Responsible Party): Acceleron Pharma Inc.

Tracking Information

• First Submitted Date: April 2, 2010
• First Posted Date: April 8, 2010
• Results First Submitted Date: May 10, 2016
• Results First Posted Date: October 14, 2016
• Last Update Posted Date: April 5, 2017
• Study Start Date: April 2010
• Actual Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 22, 2016)

• Number of Subjects With Adverse Reactions. [ Time Frame: From treatment initiation to End-of-Study Visit, approximately 24 weeks later ]
  Number of subjects in each cohort with a treatment-emergent adverse event considered at least possibly related to study drug
• Number of Subjects With Clinical Laboratory Adverse Reactions. [ Time Frame: Baseline to End-of-Study Visit, approximately 24 weeks later. ]
  Number of subjects in each cohort with treatment-emergent adverse laboratory values judged to be at least possibly related to study drug

Original Primary Outcome Measures (submitted: April 6, 2010)

• Safety and tolerability by monitoring adverse events, clinical laboratory tests, electrocardiogram (ECG), echocardiogram (ECHO), physical examinations, vital signs, and anti-drug antibodies [ Time Frame: 6 months ]
• Percent change from baseline in total body lean mass by DXA [ Time Frame: 4 months ]

Current Secondary Outcome Measures (submitted: August 22, 2016)

• Percent Change in Total Lean Body Mass by DXA Scan. [ Time Frame: Baseline to End-of-Study Visit, approximately 24 weeks later. ]
• Percent Change in Lumbar Spine Bone Mineral Density by DXA Scan. [ Time Frame: Baseline to End-of-Study Visit, approximately 24 weeks later. ]
• Percent Change in Muscle Strength Score by Hand-held Myometry. [ Time Frame: Baseline to End-of-Study Visit, approximately 24 weeks later. ]
  Manual Muscle Testing (MMT) is a procedure to measure the function and strength of individual muscles and muscle groups. Hand-held myometry, using a device known as a dynamometer, is one method used for MMT. The dynamometer is held against the patient's limb by the examiner and the patient is asked to resist the force applied by the examiner. The dynamometer measures the force applied by the patient, providing a quantitative and objective assessment of strength of the particular muscle or muscle group. The effectiveness of a therapeutic intervention on muscle strength, as measured by hand-held myometry, can be assessed by comparing post-treatment to pre-treatment (baseline) measurements.
• Change in Distance Traveled in 6 Minutes (Standardized 6-Minute-Walk Test). [ Time Frame: Baseline to End-of-Study Visit, approximately 24 weeks later. ]
  Change in distance traveled in 6 minutes (standardized 6-Minute-Walk Test); stratified by baseline age (<10 years vs. >=10 years)
• Change From Baseline in Time to Travel 10 Meters (Standardized 10-Meter-Walk/Run Test). [ Time Frame: Baseline to End-of-Study Visit, approximately 24 weeks later. ]
• Change in Pulmonary Function Tests (FVC) [ Time Frame: Baseline to End-of-Study Visit, approximately 24 weeks later. ]
  Forced Vital Capacity (FVC); 1 of 3 separate tests employed to assess pulmonary function in this study
• Change in Pulmonary Function Test (MIP) [ Time Frame: Baseline to End-of-Study Visit. approximately 24 weeks ]
  Maximum Inspiratory Pressure (MIP); 2 of 3 separate tests employed to assess pulmonary function in this study
• Change in Pulmonary Function Test (MEP) [ Time Frame: Baseline to End-of-Stuidy Visit, approximately 24 weeks ]
  Maximum Expiratory Pressure (MEP); 3 of 3 separate tests employed to assess pulmonary function in this study

Original Secondary Outcome Measures (submitted: April 6, 2010)

• Change from baseline in timed function tests [ Time Frame: 6 months ]
• Change from baseline in muscle strength tests [ Time Frame: 6 months ]
• Change from baseline in pulmonary function tests [ Time Frame: 6 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of ACE-031 in Subjects With Duchenne Muscular Dystrophy
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ACE-031 (ActRIIB-IgG1) in Subjects With Duchenne Muscular Dystrophy
• Brief Summary: The purpose of this study is to determine if ACE-031 is safe and well-tolerated in boys with Duchenne Muscular Dystrophy (DMD) and to select the optimal doses of ACE-031 in terms of safety and pharmacodynamic (PD) activity for designing future studies. [Note: This study was terminated based on safety data]
• Detailed Description: ACE-031, a soluble form of the human activin receptor type IIB, was administered once every 2 to 4 weeks by subcutaneous (SC) injection to boys with DMD. Dose levels and regimens for this multiple-dose study were based on data from the initial clinical studies in healthy subjects in which doses of 0.02 to 3 mg/kg SC were evaluated. A total of 24 subjects were enrolled into the study; 18 received ACE-031 and 6 placebo. All subjects were treated for a period of 12 weeks.The pharmacodynamic effects of ACE-031 treatment were assessed by a battery of motor function test that included the 6-Minute Walk Test, the 10-Minute Walk/Run Test, the 4-Stair Climb Test and the Gower Maneuver (GW). Muscle strength was assessed by hand-held myometry and fixed system testing. Body composition (i.e., spine BMD, lean mass, and fat mass) was assessed by whole body and lumbar spine DXA scans. Pulmonary function was assessed by forced vital capacity (FVC), maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP). ACE-031 safety was evaluated through observation of the incidence and severity of adverse events.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Duchenne Muscular Dystrophy

Intervention

• Biological: ACE-031 0.5 mg/kg q4wk
  ACE-031 0.5 mg/kg subcutaneously once every 4 weeks for 12 weeks.
• Biological: ACE-031 1.0 mg/kg q2wk
  ACE-031 1.0 mg/kg subcutaneously once every 2 weeks for 12 weeks.
• Other: Placebo
  Matching volume placebo subcutaneously every 2 or 4 weeks for 12 weeks.

Study Arms

• Experimental: ACE-031 0.5 mg/kg q4wk
  Intervention: Biological: ACE-031 0.5 mg/kg q4wk
• Experimental: ACE-031 1.0 mg/kg q2wk
  Intervention: Biological: ACE-031 1.0 mg/kg q2wk
• Placebo Comparator: Placebo
  Intervention: Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: April 19, 2011): 24
• Original Estimated Enrollment (submitted: April 6, 2010): 76
• Actual Study Completion Date: June 2011
• Actual Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Diagnosis of DMD confirmed
• Ambulant
• Corticosteroid therapy for at least one year prior to study day 1 and on a stable dose and schedule for at least 6 months prior to study day 1
• Evidence of muscle weakness by clinical assessment

Exclusion Criteria:

• Any previous treatment with another investigational product within 6 months prior to study day 1
• Any clinically significant cardiac, endocrine, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease that is not related to DMD
• Inability to perform a whole body dual x-ray absorptiometry (DXA) scan

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 4 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada

Administrative Information

• NCT Number: NCT01099761
• Other Study ID Numbers: A031-03
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: Abstract summarizing trial data has been published online in Muscle & Nerve 23-Dec-2016 https://www.ncbi.nlm.nih.gov/pubmed/27462804 The Sponor currently has no plans to make IPD available for a number of reasons; (i) the study was terminated by the Sponsor prematurely based upon concerns for potential adverse drug reactions following long-term use, which were identified in chronic toxicity studies in animals, (ii) the study population was one with a rare disease, in a groups of subjects with a relatively narrow age range, across a small number of study sites. The Sponsor believes that these factors, taken together, make patient anonymity a significant challenge.

• Responsible Party: Acceleron Pharma Inc.
• Study Sponsor: Acceleron Pharma Inc.
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Acceleron Pharma Inc.
• Verification Date: March 2017